Activity of Mu and Pi Glutathione S-Transferase isoenzymes in triclabendazole susceptible and resistant Fasciola hepatica strains.

FERNÁNDEZ V.; CADENAZZI G.; ORTIZ OBRITAS P.; SOLANA M.; SANSINANEA A.; SOLANA H.

Noordwijkerhout

Congreso; 12th International Congress of the European Association for Veterinary Pharmacology and Toxicology; 2012

INTRODUCTIONFasciolosis produced by the trematode Fasciola hepatica is aneconomically important disease of livestock which is controlledby the anthelmintic triclabendazole. Triclabendazole (TCBZ) ismetabolized into its active sulphoxide metabolite (TCBZSO) bythe host liver but also by the parasite. Resistance to TCBZ isassociated with an enhanced metabolic activity carried on by amultienzymatic action involving more than one metabolicpathway as demonstrated in our laboratory (1). GlutathioneS-transferase (GST) enzymes are involved in the detoxificationof endogenous and xenobiotic compounds through glutathioneconjugation or glutathione peroxidase activity and differentGST-isoenzymes may have different metabolic activity. In thepresent work we evaluated the cytosolic activity of total GST,GST-mu and GST-pi-isoenzymes in TCBZ-susceptible (Cullompton)and TCBZ-resistant (Sligo and Oberon) adult Fasciolahepatica strains.MATERIALS AND METHODSNine parasite-free Corriedale weaned lambs were each orallyinfected with 200 metacercariae of Fasciola hepatica, three withthe Cullompton strain, three with the Sligo strain and threewith the Oberon strain. Sixteen weeks after the infection, theflukes were collected and processed to obtain the cytosolicfractions (2), and the GST activity was determined as describedelsewhere (3).RESULTSThe total GST activity (n = 5) in Sligo (1277 ± 32 nmol min)1mg)1 protein) and Oberon (1216 ± 16 nmol min)1 mg)1 protein)resistant strains was 59% and 52% respectively higher(P < 0.001) than in the Cullompton susceptible strain(800 ± 60 nmol min)1 mg)1 protein). While GST-pi activity(substrate: Ethacrynic acid) did not differ between the differentstrains tested, the GST-mu activity (substrate: DCNB) in Oberonand Sligo resistant strains was 17% and 26% respectivelyhigher than in the Cullompton susceptible strain,confirming itsresponsability in the expression of the highest metabolicactivity of total GST. This higher GST activity has potentialrelevance as it might contribute to the phenomenon ofresistance to TCBZ.